WASHINGTON - July 19 - The Food and Drug Administration (FDA) and the Office for Human Research Protections (OHRP), which is housed in the U.S. Department of Health and Human Services, should suspend studies of a dangerous drug and promptly investigate allegations that these studies are unethical and fail to comply with federal regulations that protect human subjects, Public Citizen said today in letters to the two agencies.

One of the studies involves children, which raises serious ethical concerns and appears to violate special federal regulations designed to protect children in research, said Dr. Michael Carome, deputy director of Public Citizen’s Health Research Group. The drug, canakinumab, also known as Ilaris, is manufactured by Novartis and approved by the FDA only for treating a group of rare serious genetic disorders called cryopyrin-associated periodic syndromes, which cause widespread inflammation in the body.

Public Citizen told an FDA advisory committee in June that it should not approve the drug for treatment of gouty arthritis attacks. The advisory committee agreed and voted against approval. Now, the FDA should investigate the ongoing studies, which are testing the drug in subjects with such conditions as heart disease and diabetes, the letters said.

“Since even a single dose of canakinumab has many serious risks, including the known risk of life-threatening infections and possibly cancer due to suppression of the immune system, further clinical trials of this drug should proceed only if there is a reasonable basis justifying these great risks to subjects,” Carome said. “For at least two of the ongoing studies, such a justification is lacking.”

The studies Public Citizen cited in its letters are unnecessarily risky for the subjects, yet the FDA was aware of and possibly endorsed the trials.
Public Citizen is calling upon the FDA and OHRP to suspend the two studies pending the outcome of their investigations.

In one study sponsored by Novartis, which started in April 2011, 7,200 adult patients who have had heart attacks are being given injections of canakinumab or a placebo every three months. The subjects are to be followed for three years to see if the drug decreases the chances of further heart attacks, strokes and death from cardiovascular disease.

However, given the apparent lack of any preliminary data regarding potential benefits of this dangerous drug in preventing heart attacks and strokes, there is no reasonable justification for initiating such a large trial in heart attack patients, and the known risks of the research do not outweigh the expected benefits, Carome said.

In a different study funded by the National Institutes of Health, 66 patients, ranging in age from six to 45 years old, with newly diagnosed type-1 diabetes are being given monthly injections of canakinumab or a placebo for one year to see if their pancreases still produce insulin. The study began in October 2010.

In this second study, the involvement of children raises additional serious ethical and regulatory concerns, Carome said. The significant risks of monthly canakinumab injections are not offset by any prospect of reasonably foreseeable benefits to the children, which may be a violation of research standards, Carome said.

Public Citizen also is asking the FDA to assess all other ongoing clinical trials involving canakinumab to determine whether the predictable risks to subjects outweigh the potential benefits of the research.
A search of the website ClinicalTrials.gov shows that Novartis also is conducting studies of canakinumab in subjects with type-2 diabetes, osteoarthritis and polymyalgia rheumatica, among others, with several studies involving repeated dosing over a prolonged time period.

“Just one dose of canakinumab has many serious risks. The dangers of taking this drug will only be magnified in human subjects exposed to multiple doses over a prolonged period of time,” Carome said.